Where Scientific Innovation, Discovery and Clinical Dermatology Converge

Dr. Michael Rosenblum, PhD is a 2023 DF Stiefel Scholar, Professor of Dermatology, School of Medicine, and Senior Associate Vice-Chair of Research, UCSF Department of Dermatology.

Michael Rosenblum, MD, PhD, was a 20-year-old undergraduate at the University of British Columbia when his mother became ill with breast cancer. At the time, physician-scientists were just beginning to explore how the immune system could be directed to target cancer cells. At the forefront was Dr. Steven Rosenberg, who had written a book that struck a chord with the young biologist, who decided he wanted to study the immune system.

“After reading The Transformed Cell, I wrote to Dr. Rosenberg to tell him I wanted to understand how the immune system can fight cancer,” Dr. Rosenblum said. “He wrote back, which surprised me given he was chief of the Surgery Branch at the National Cancer Institute. He told me I should get an MD because it would open doors to do medical research.”

Dr. Rosenblum went on to pursue an MD, PhD at the Medical College of Wisconsin, chosen in part because of its proximity to his home in Windsor, Ontario so he could be close enough to easily visit his ailing mother. Following his doctorate in immunology he thought he would specialize in hematology-oncology, given his family connection with cancer, but soon learned how difficult it is to do research with really sick patients. After meeting Kim Yancey, MD, who was chair of dermatology at the Medical College of Wisconsin at the time, he realized he could combine his love of immunology with a discipline much more suited to the type of clinical research that interested him.

“I went into dermatology for research and relied heavily on Dr. Kim Yancey’s mentorship,” Dr. Rosenblum said. “As a physician I wanted to care for patients with bad inflammatory skin diseases. I saw firsthand how horrible it could be with respect to quality of life, and even mortality. But I also recognized that immunology of the skin was a wide-open research space. Immunology was advanced in other organ systems and other disciplines, but in dermatology there was a readily available niche.”

He chose to do his residency at the University of California, San Francisco (UCSF) for three reasons. “The school has a great dermatology program, immunology at UCSF is first-rate, and my sister was living in San Francisco. I got along with everybody and thought it was a good fit for me. Fortunately, they thought I was a good fit too.”

He combined his residency with a postdoctoral fellowship at UCSF in the physician-scientist training track. He trained in the lab of Dr. Abul Abbas, joined the UCSF faculty in 2012, and took over running the lab when Dr. Abbas retired soon after. Dr. Rosenblum currently sees patients with chronic inflammatory skin diseases one half-day each week, spending the remainder of his time in the lab exploring how the immune system works in the skin.

Tregs and AD

Dr. Rosenblum’s lab investigates regulatory T cells (Tregs) and how the regulatory arm of the immune system functions in healthy and diseased skin, with the hope that this understanding can lead to the development of new treatments for autoimmune skin diseases. Tregs in the skin help regulate hair follicle cycling, repair of the epidermis, and fibroblast interactions. Much of the work in his lab focuses on how Tregs control effector T cells, which are responsible for fighting microbial infections. The Rosenblum Lab has pinpointed ways this regulation, which leads to a balanced immune system, can go awry, resulting in chronic inflammatory disease. For example, Tregs have been shown to protect hair follicles from inflammation in a mouse model, a finding with potential implications for autoimmune skin diseases, like alopecia (Cohen et al. 2024).

Dr. Rosenblum’s laboratory team returning from a hike on the Sonoma Coast during their retreat.
(L to R) Maggie Lowe, Priscila Munoz Sandoval, Josh Moreau, Jarish Cohen, Courtney Macon, Irek Habrylo, Victoire Gouirand, Mike Rosenblum, Madison Moss, Ian Boothby, and Maxime Kinet

“All chronic inflammatory disease of the skin results from an imbalance in which there are too many effector cells attacking self-antigens instead of foreign infectious particles,” he said. “This overwhelms the regulatory arm. By learning how the regulatory cells function, we can figure out ways to improve regulation and rebalance the inflammation.”

Dr. Rosenblum is proud that some of the newest treatments in atopic dermatitis are regulatory T-cell therapies. He referred to positive evidence from a phase 1b clinical trial for rezpegaldesleukin, one of the first drugs to augment Tregs for the treatment of atopic dermatitis (Nektar 2023).

“By learning how the regulatory cells function, we can figure out ways to improve regulation and rebalance the inflammation.”

“This is just the tip of the iceberg,” Dr. Rosenblum said. “Many more therapies will come down the pipeline and are going to improve on this first attempt. It’s exciting to know all the work we’re doing is now being translated for clinical benefit. I’ve been around long enough to see this and that’s super exciting for me.”

Dr. Rosenblum was a keynote speaker, alongside fellow Stiefel Scholars Drs. Aimee Payne and John Harris, at the 2023 DF Clinical Symposium. He spoke about recent findings using a mouse model to unravel the role fibroblasts play in the immune system and in the context of healthy and diseased skin (Rosenblum 2023). His lab is pursuing translational research applications for human skin diseases, including eosinophilic fasciitis and atopic dermatitis.

HS Center of Excellence

“If I’m going to spend time on something medically, it has to be meaningful for me,” Dr. Rosenblum said. “HS is really high on that list. If you ask most dermatologists what disease they would never want to get, it’s HS. It’s a horribly morbid disease. It’s a hard disease to live with and it’s a hard disease to treat. I want to find treatments for this.”

Dr. Rosenblum helped establish an HS Center of Excellence at UCSF, including recruiting an expert in HS, Dr. Haley Naik. The center provides cutting-edge care for patients and does translational research.

To this end, he helped establish an HS Center of Excellence at UCSF, including recruiting an expert in HS, Dr. Haley Naik. The center provides cutting-edge care for patients and does translational research. Dr. Rosenblum’s lab uses patient biopsies, RNA sequencing and transcriptomics, and other techniques to understand the factors driving this disease. Among many findings, they’ve shown that tertiary lymphoid structures capable of sustaining B cells exist in HS lesions, supporting the hypothesis that modulation of B cells may have therapeutic benefit in the disease (Lowe et al. 2023).

Innovation advances treatment

While scientists like him do research really well, Dr. Rosenblum understands there has to be a partnership where the academic and the basic science merge to take discoveries to the next step and make drugs that will be made widely available to help patients.

Given his lab’s focus on HS, the unmet medical need for good treatments, the supportive infrastructure at UCSF, and the innovative environment in the Bay Area, Dr. Rosenblum has done a lot of work to bring the benefits of the work done in his research lab to further the treatments available to patients. His work with HS is a perfect example. “We’re discovering new cell types in this disease to target. I’m optimistic this type of approach will lead to a whole armamentarium of therapies for people with HS.”

Transformational support

Dr. Rosenblum received a fellowship from the Dermatology Foundation in 2009, a three-year Career Development Award in 2010, and was named a Stiefel Scholar in 2015, an award for exceptional mid-career physician-scientists that came with three years of research funding.

“[DF] is a huge shining star, and I just don’t know if other disciplines have anything like it. I tell them, it’s going to be a lot harder for you without this body to hold your hand through what will be a really critical period.”

“The support of the Foundation was transformational, focused as it was on the period in my career trajectory that was the most fragile time,” Dr. Rosenblum said. “They understand how difficult it can be after all that training to get your career started and become an independent physician-scientist. I was trying to play in a sandbox full of people with name recognition and experience who had been there for a long time.”

Whenever an aspiring physician-scientist asks him whether they should choose dermatology as their specialty, he is quick to mention the Foundation as an incentive.

“It’s a huge shining star, and I just don’t know if other disciplines have anything like it. I tell them, it’s going to be a lot harder for you without this body to hold your hand through what will be a really critical period. They are the reason why we have these new therapies coming down the pipeline. None of this innovation would have happened, because people like me wouldn’t have been able to establish our careers.”

As a way to say thank you, Dr. Rosenblum has been active within the Foundation for more than ten years as a volunteer and as a member of the Scholars Circle and the Leaders’ Society.

“I want to give back because they’re the ones who have really helped me when I needed it. I also want to see new investigators supported the way I was.”

As the Foundation celebrates its 60th anniversary, Dr. Rosenblum thinks its current role is to ensure the specialty has future leaders focused on the science, the mechanisms of disease, and developing new therapies.

As a way to say thank you, Dr. Rosenblum has been active within the Foundation for more than ten years as a volunteer and as a member of the Scholars Circle and the Leaders’ Society.

“The Dermatology Foundation will have a larger role moving forward as people are drawn away from basic science and translational research in dermatology due to how funds flow and the status of reimbursement,” he said. “Healthcare costs are rising and the first thing to get pinched is research and development.”

The future is translational

Dr. Rosenblum believes dermatologists will be at the forefront of translational research that leads to innovative treatments over the next few decades, in large part because they have ready access to diseased tissue to study.

“We’re fortunate to study the most accessible organ,” he said. “We’re beginning to appreciate that mouse models are not helping as much as we hoped to discover pathways relevant to human disease. The pendulum has swung in the direction that, to understand and treat human disease, we have to study human disease. And to do that, you need access to diseased tissue.”

One way his lab combines the best of both approaches is to use humanized mice. They graft human skin onto the backs of mice, which allows them to study human skin in an intact animal without needing to do an expensive clinical trial or interventional study in humans.

Dr. Rosenblum believes dermatologists will be at the forefront of translational research that leads to innovative treatments over the next few decades, in large part because they have ready access to diseased tissue to study.

By combining his clinical practice, research in the lab, and entrepreneurship, Dr. Rosenblum will no doubt continue to lead the way to discoveries of innovative, effective therapies for diseases dermatologists consider high on the list of those needing better treatments.

Register today for the 2025 Clinical Symposium.

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